Fahim Asmaa M, Ismael Eman H I, Elsayed Ghada H, Farag Ahmad M
Department of Green Chemistry, National Research Center, Dokki, Cairo, Egypt.
Department of Organometallic and Organ Metalloid Chemistry, National Research Centre, Dokki, Cairo, Egypt.
J Biomol Struct Dyn. 2022;40(19):9177-9193. doi: 10.1080/07391102.2021.1930582. Epub 2021 Jun 9.
In this investigation, we studied the reactivity of 5-aminouracil () with ethyl cyanoacetate () utilizing microwave irradiation to afford the corresponding 2-cyano--(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)acetamide () in excellent yield. The electrophilic azo-coupling reaction of acetamide with aromatic diazonium salts afforded the corresponding hydrazone derivatives The Michael addition cyclization of hydrazone in pyridine to give pyrazolo[5,1-c][1, 2, 4]triazine-3-carboxamide derivatives. The obtained compounds were elucidated against antimicrobial activity and antitumor activity breast cancer cells (MCF-7) and liver cancer cells (HepG2) utilized MTT assay. Compounds , and revealed more inhibitory influence on MCF7 and HepG2 growth than the reference drug doxorubicin (Dox) after 48 h incubation. Furthermore, molecular docking studies were carried out on one of the most effective compound 4-amino-N-(2,4-dioxo-1,2,3,4-tetrahydropyrimidin-5-yl)-7-(4-fluorophenyl) pyrazole [5,1-c][1, 2, 4]triazine-3-carboxamide (5c) (TFC) with (PDB: 3t88), (PDB: 2wje) , (PDB: 4ynt), (PDB: 1tgh), (PDB: 4hdq) and (PDB: 3pxe) which attached with different proteins with different energies and shortage bond distance. Also; the comprehensive theoretical and experimental mechanical studies of compound and were compatible with FTIR and H NMR spectral data. The optimized molecular structure of with FTIR was examined via DFT/ B3LYP/6-31G (d) level.Communicated by Ramaswamy H. Sarma.
在本研究中，我们利用微波辐射研究了5-氨基尿嘧啶（）与氰基乙酸乙酯（）的反应活性，以优异的产率得到相应的2-氰基-（2,4-二氧代-1,2,3,4-四氢嘧啶-5-基）乙酰胺（）。乙酰胺（）与芳族重氮盐的亲电偶氮偶联反应得到相应的腙衍生物（）。腙在吡啶中的迈克尔加成环化反应得到吡唑并[5,1-c][1,2,4]三嗪-3-甲酰胺（）衍生物。利用MTT法对所得化合物进行了抗微生物活性以及对乳腺癌细胞（MCF-7）和肝癌细胞（HepG2）的抗肿瘤活性研究。在孵育48小时后，化合物（）、（）和（）对MCF7和HepG2生长的抑制作用比参考药物阿霉素（Dox）更强。此外，对最有效的化合物之一4-氨基-N-（2,4-二氧代-1,2,3,4-四氢嘧啶-5-基）-7-（4-氟苯基）吡唑并[5,1-c][1,2,4]三嗪-3-甲酰胺（5c）（TFC）与（PDB：3t88）、（PDB：2wje）、（PDB：4ynt）、（PDB：1tgh）、（PDB：4hdq）和（PDB：3pxe）进行了分子对接研究，这些蛋白与不同的蛋白质以不同的能量和短键距结合。此外，化合物（）和（）的综合理论和实验力学研究与FTIR和H NMR光谱数据相符。通过DFT/B3LYP/6-31G（d）水平对（）的FTIR优化分子结构进行了研究。由拉马斯瓦米·H·萨尔马通讯。
